This research project would study the mechanisms of transduction used by olfactory cells to detect and discriminate chemical substances. Its long term objectives are to describe the physiological basis of the sense of smell. the initial steps in detecting and distinguishing chemical compounds occur in the peripheral olfactory neurons found in the upper respiratory pathway. These cells encode information about odorants and transmit it to the brain in trains of action potentials. Odorants appear to modulate the generator potential that produces action potentials in olfactory neurons by activating transduction mechanisms. The project will employ olfactory tissue from Necturus maculosus, a salamander with exceptionally large cells. A systematic series of measurements on the intact epithelium using extracellular recordings will be undertaken to identify compounds to which the animal is sensitive. The membrane properties and the physiological response to odorants will be studied in single neurons with both patch-clamp and intracellular voltage-clamp methods. Both mature and immature neurons will be studied in order to minimize problems related to substrate specificity and to evaluate the development of chemical discrimination. The specific aims of the project are: 1. Identify a group of chemical compounds to which the animal is sensitive in vivo. 2. Characterize the cellular mechanisms used for substrate detection by mature and immature olfactory cells. Correlate the action of these mechanisms with specific types of ion channels and the components of the membrane current. Determine whether/how second messenger systems contribute to these mechanisms by regulating the membrane conductance. 3. Evaluate the cellular basis of chemical discrimination. Determine the overlap and distribution of chemical sensitivities in individual olfactory neurons. Define the division of discriminatory functions between the peripheral and central portions of the olfactory system.